Development of bioorthogonal SERS imaging probe in biological and biomedical applications

ABSTRACT Living-cell imaging demands high specificity, sensitivity, and minimal background interference to the targets of interest. However, developing a desirable imaging probe that can possess all the above features is still challenging. The bioorthogonal surface-enhanced Raman scattering (SERS) imaging has been recently emerged through utilizing Raman reporters with characteristic peaks in Raman-silent region of cells (1800-2800 cm−1), which opens a revolutionary avenue for living-cell imaging with multiplexing capability. In this review, we focus on the recent advances in the technology development and the biological and biomedical applications of the living-cell bioorthogonal SERS imaging technique. After introduction of fundamental principles for bioorthogonal tag or label, we present applications for visualization of various intracellular components and environment including proteins, nucleic acids, lipids, pH and hypoxia, even for cancer diagnosis in tissue samples. Then, various bioorthogonal SERS imaging-guided therapy strategies have been discussed such as phototherapy and surgery. In conclusion, this strategy has great potential to be a flexible and robust tool for visualization detection and diseases diagnosis.

活细胞成像要求对目标具有高特异性和高灵敏度，并尽量减少背景干扰。然而，同时满足这些要求的理想成像探针仍然难以开发。近年来，生物正交表面增强拉曼散射（SERS）成像利用在细胞拉曼沉默区（1800-2800 cm−1）具有特征峰的拉曼报告分子，为具备多重检测能力的活细胞成像开辟了新途径。本综述聚焦于活细胞生物正交 SERS 成像技术的发展，以及其在生物学和生物医学领域的应用进展。在介绍生物正交标签或标记的基本原理后，文章总结了该技术在蛋白质、核酸、脂质、pH 和缺氧等细胞内成分与微环境可视化方面的应用，也讨论了其在组织样本癌症诊断中的潜力。随后，综述了生物正交 SERS 成像引导的光疗和手术等治疗策略。总体而言，该策略有望成为可视化检测和疾病诊断中灵活而可靠的工具。